A critical area in current efforts to understand the mechanism of cellular control and development is the nature and operation of protein-nucleic acid interactions. The basic objective of this proposal is the design and synthesis of water soluble, cleavable, photo-activated, site-specific heterobifunctional protein-nucleic acid cross-linking reagents which can be used as molecular tools to probe the structure of protein-nucleic acid complexes. A second objective is the synthesis of bifunctional interhelical nucleic acid-nucleic acid cross-linkers in order to examine the nature of DNA and RNA packaging in vivo.